Nervous system conditions ranging from acute injuries such as spinal cord injuries to neurodegenerative diseases such as Alzheimer's disease have been and continue to be among the most intractable health conditions. Thus, there is an ongoing need for disease models and screening systems to identify effective therapies for treating neuronal dysfunction.
The Drosophila larval neuromuscular junction (NMJ) has been a powerful model system for uncovering and characterizing genetic and molecular mechanisms that regulate axonal and synaptic growth, structure, and function. The NMJ offers advantageous features for neurogenetic analyses including a segmentally repeated and stereotypic morphology, which allows easy quantification of morphological and functional properties. In addition, the molecular mechanisms that regulate synapse formation and function are conserved between vertebrates and Drosophila. However, despite these advantages, the short duration of the third instar stage, which lasts only about three days, has limited the use of the larval NMJ as a model system for time-dependent studies. Thus, the larval NMJ is not well-suited for studying biological mechanisms, such as neurodegeneration or nerve regeneration that generally occur over longer time intervals. In principle, this constraint could be overcome if the duration of the larval period could be extended without causing significant perturbations of NMJ structure and function. The mechanisms that maintain NMJ structure over time, how synapses change with age or disease, and long-term effects of neuronal injury could then be investigated in these larvae.